1-methyl-1,4-diazepane -Drug Synthesis Database

【结构式】

【分子编号】20903

【品名】1-methyl-1,4-diazepane

【CA登记号】4318-37-0

【分子式】C₆H₁₄N₂

【分子量】114.19064

【元素组成】C 63.11% H 12.36% N 24.53%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

By reaction of 1-methylhomopiperazine (I) with CS2 in ether.

参考文献中间体

合成目标

【1】 Carlsson, A.E.; et al.; SE 345270 .
【2】 Carlsson, A.E.; et al.; DE 1810664 .
【3】 Amit, Z.; Ogren, S.-O.; US 4131671 .
【4】 Castaner, J.; Paton, D.M.; FLA-57. Drugs Fut 1980, 5, 6, 288.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	20903	1-methyl-1,4-diazepane	4318-37-0	C₆H₁₄N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

A new synthesis of KB-2413 has been described: The reaction of 2-chloronitrobenzene (I) with 2-ethoxyethylamine (II) gives 1-(2-ethoxyethylamino)-2-nitrobenzene (III), which is reduced with Zn and NaOH to N-(2-ethoxyethyl-o-phenylenediamine (IV). The cyclization of (IV) with urea in amyl alcohol affords 1-(2-ethoxyethyl)benzimidazol-2-one (V), which is treated with refluxing POCl3 yielding 2-chloro-1-(2-ethoxyethyl)benzimidazole (VI). Finally, this compound is condensed with N-methylhexahydro-1,4-diazepine (VII) and treated with fumaric acid.

参考文献中间体

合成目标

【1】 Awata, N.; Satomi, O.; Synthesis of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)-[2-14C]benzimidazole difumarate ([14C]KB-2413). J Label Compd Radiopharm 1987, 24, 3, 331-8.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	15248	1-chloro-2-nitrobenzene	88-73-3	C₆H₄ClNO₂	详情	详情
(II)	20898	2-ethoxyethylamine; 2-ethoxy-1-ethanamine	110-76-9	C₄H₁₁NO	详情	详情
(III)	20899	N-(2-ethoxyethyl)-N-(2-nitrophenyl)amine; N-(2-ethoxyethyl)-2-nitroaniline		C₁₀H₁₄N₂O₃	详情	详情
(IV)	20900	N(1)-(2-ethoxyethyl)-1,2-benzenediamine; N-(2-aminophenyl)-N-(2-ethoxyethyl)amine		C₁₀H₁₆N₂O	详情	详情
(V)	20901	1-(2-ethoxyethyl)-1,3-dihydro-2H-benzimidazol-2-one		C₁₁H₁₄N₂O₂	详情	详情
(VI)	20902	2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole; 2-(2-chloro-1H-benzimidazol-1-yl)ethyl ethyl ether		C₁₁H₁₃ClN₂O	详情	详情
(VII)	20903	1-methyl-1,4-diazepane	4318-37-0	C₆H₁₄N₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

The reaction of 2-chlorobenzimidazole (I) with 2-chloroethyl ethyl ether (II) by means of NaOH in DMF gives 1-(2-ethoxyethyl)benzimidazole (III), which is then condensed with N-methylhomopiperazine (IV) at 120 C.

参考文献中间体

合成目标

【1】 Iemura, R.; et al. (Kanebo Pharmaceuticals, Ltd.); Benzimidazole derivatives, process for the peparation thereof and pharmaceutical composition containing the same. EP 0079545; JP 58079983 .
【2】 Serradell, M.N.; Castaner, J.; KB-2413. Drugs Fut 1985, 10, 5, 397.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	26761	2-chloroimidazo[1,2-a]pyridine; 2-chlorobenzimidazole; 2-Amino-4'-chlorodiphenylether; 2-Aminodiphenylether; 2-chloro-1H-benzimidazole	4857-06-1	C₇H₅ClN₂	详情	详情
(II)	29358	1-chloro-2-ethoxyethane	628-34-2	C₄H₉ClO	详情	详情
(III)	20902	2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole; 2-(2-chloro-1H-benzimidazol-1-yl)ethyl ethyl ether		C₁₁H₁₃ClN₂O	详情	详情
(IV)	20903	1-methyl-1,4-diazepane	4318-37-0	C₆H₁₄N₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

2-Chlorobenzimidazole (I) was treated with NaH in DMF and the resulting sodium salt was alkylated with 4-[2-(2-chloroethoxy)ethoxy]-2,3,6-trimethylphenol (II) to give (III). Subsequent displacement of the chlorine of (III) with N-methyl homopiperazine (IV) at 130 C produced the desired 2-(homopiperazino)benzimidazole, which was finally treated with fumaric acid in EtOH to yield the corresponding bis fumarate salt.

参考文献中间体

合成目标

【1】 Nakano, H.; Inoue, T.; Inagaki, N.; Taguchi, T.; Satoh, T.; Kawasaki, N.; Nagai, H.; Matsumoto, H.; Miyataka, H.; Synthesis and biological activities of novel antiallergic agents with 5-lipoxygenase inhibiting action. Bioorg Med Chem 2000, 8, 2, 373.
【2】 Nakano, H.; Inoue, T.; Inagaki, N.; Taguchi, T.; Matsumoto, H.; Satoh, T.; Miyataka, H.; Kawasaki, N.; Synthesis of benzimidazole derivatives as antiallergic agents with 5-lipoxygenase inhibiting action. Chem Pharm Bull 1999, 47, 11, 1573.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	26761	2-chloroimidazo[1,2-a]pyridine; 2-chlorobenzimidazole; 2-Amino-4'-chlorodiphenylether; 2-Aminodiphenylether; 2-chloro-1H-benzimidazole	4857-06-1	C₇H₅ClN₂	详情	详情
(II)	38944	4-[2-(2-chloroethoxy)ethoxy]-2,3,6-trimethylphenol		C₁₃H₁₉ClO₃	详情	详情
(III)	38945	4-[2-[2-(2-chloro-1H-benzimidazol-1-yl)ethoxy]ethoxy]-2,3,6-trimethylphenol		C₂₀H₂₃ClN₂O₃	详情	详情
(IV)	20903	1-methyl-1,4-diazepane	4318-37-0	C₆H₁₄N₂	详情	详情

Extended Information